Project Summary The upgrade that is the subject of this proposal is aimed at providing multinuclear Magnetic Resonance (MR) capabilities for a Biograph mMR (PET/MR) at the Department of Radiology. This state-of-the-art whole-body human scanner can acquire simultaneous magnetic resonance (MR) and positron emission tomography (PET) images. The relative strengths and weaknesses of the two modalities are both synergistic and complementary. MR images provide unmatched soft tissue details, while PET images can evaluate the metabolism of a particular organ or tissue in order to assess its physiology. Therefore, this hybrid PET/MR system can capture activity and anatomy together offering researchers and clinicians a more precise and accurate assessment of disease, as well as an improved understanding of the physiologic process. Our current PET/MR system is restricted to 1H MR studies, which significantly limits the ?window? of observation by eliminating other biologically relevant nuclei such as 23Na, and 31P. These nuclei are involved in major physiological processes of mammalian cells. For example tissue sodium levels are altered by cellular integrity and energy status in living animal cells. A low intracellular sodium concentration is maintained by actively pumping sodium out of the cell with the Na+/K+ATP-ase pump. If ATP supply is insufficient because the cellular energy metabolism is impaired or challenged, or if the cell membrane integrity is compromised, the intracellular sodium levels rise sharply. Such physiological processes can be assessed by various MR techniques to gain insights into the metabolism of cells in vivo. Therefore, the proposed multinuclear upgrade of our PET/MR system will provide an unprecedented means to simultaneously assess morphological, functional, and molecular information in the human body, and be particularly useful for neurological, oncological, and cardiovascular studies. At least 12 NIH-funded projects would benefit from this upgrade. Based on our currently funded research projects, we expect this upgrade to bring new insights into the underlying mechanisms of many neurological conditions (e.g., Alzheimer's disease, multiple sclerosis, and traumatic brain injury), improved understanding of the effects of metabolic disorders such as diabetes in the brain and the skeletal muscle, as well as increased specificity in tumor detection.